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Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice

Notopterol is a naturally occurring furanocoumarin compound found in the root of Notopterygium incisum. Hyperuricemia involves the activation of chronic inflammation and leads to cardiac damage. Whether notopterol has cardioprotective potential in hyperuricemia mice remains elusive. The hyperuricemi...

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Autores principales: Wang, Qian, Peng, Dewei, Huang, Bingyu, Men, Lintong, Jiang, Tao, Huo, Shengqi, Wang, Moran, Guo, Junyi, Lv, Jiagao, Lin, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052463/
https://www.ncbi.nlm.nih.gov/pubmed/36986461
http://dx.doi.org/10.3390/ph16030361
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author Wang, Qian
Peng, Dewei
Huang, Bingyu
Men, Lintong
Jiang, Tao
Huo, Shengqi
Wang, Moran
Guo, Junyi
Lv, Jiagao
Lin, Li
author_facet Wang, Qian
Peng, Dewei
Huang, Bingyu
Men, Lintong
Jiang, Tao
Huo, Shengqi
Wang, Moran
Guo, Junyi
Lv, Jiagao
Lin, Li
author_sort Wang, Qian
collection PubMed
description Notopterol is a naturally occurring furanocoumarin compound found in the root of Notopterygium incisum. Hyperuricemia involves the activation of chronic inflammation and leads to cardiac damage. Whether notopterol has cardioprotective potential in hyperuricemia mice remains elusive. The hyperuricemic mouse model was constructed by administration of potassium oxonate and adenine every other day for six weeks. Notopterol (20 mg/kg) and allopurinol (10 mg/kg) were given daily as treatment, respectively. The results showed that hyperuricemia dampened heart function and reduced exercise capacity. Notopterol treatment improved exercise capacity and alleviated cardiac dysfunction in hyperuricemic mice. P2X7R and pyroptosis signals were activated both in hyperuricemic mice and in uric acid-stimulated H9c2 cells. Additionally, it was verified that inhibition of P2X7R alleviated pyroptosis and inflammatory signals in uric acid-treated H9c2 cells. Notopterol administration significantly suppressed expression levels of pyroptosis associated proteins and P2X7R in vivo and in vitro. P2X7R overexpression abolished the inhibition effect of notopterol on pyroptosis. Collectively, our findings suggested that P2X7R played a critical role in uric acid-induced NLRP3 inflammatory signals. Notopterol inhibited pyroptosis via inhibiting the P2X7R/NLRP3 signaling pathway under uric acid stimulation. Notopterol might represent a potential therapeutic strategy against pyroptosis and improve cardiac function in hyperuricemic mice.
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spelling pubmed-100524632023-03-30 Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice Wang, Qian Peng, Dewei Huang, Bingyu Men, Lintong Jiang, Tao Huo, Shengqi Wang, Moran Guo, Junyi Lv, Jiagao Lin, Li Pharmaceuticals (Basel) Article Notopterol is a naturally occurring furanocoumarin compound found in the root of Notopterygium incisum. Hyperuricemia involves the activation of chronic inflammation and leads to cardiac damage. Whether notopterol has cardioprotective potential in hyperuricemia mice remains elusive. The hyperuricemic mouse model was constructed by administration of potassium oxonate and adenine every other day for six weeks. Notopterol (20 mg/kg) and allopurinol (10 mg/kg) were given daily as treatment, respectively. The results showed that hyperuricemia dampened heart function and reduced exercise capacity. Notopterol treatment improved exercise capacity and alleviated cardiac dysfunction in hyperuricemic mice. P2X7R and pyroptosis signals were activated both in hyperuricemic mice and in uric acid-stimulated H9c2 cells. Additionally, it was verified that inhibition of P2X7R alleviated pyroptosis and inflammatory signals in uric acid-treated H9c2 cells. Notopterol administration significantly suppressed expression levels of pyroptosis associated proteins and P2X7R in vivo and in vitro. P2X7R overexpression abolished the inhibition effect of notopterol on pyroptosis. Collectively, our findings suggested that P2X7R played a critical role in uric acid-induced NLRP3 inflammatory signals. Notopterol inhibited pyroptosis via inhibiting the P2X7R/NLRP3 signaling pathway under uric acid stimulation. Notopterol might represent a potential therapeutic strategy against pyroptosis and improve cardiac function in hyperuricemic mice. MDPI 2023-02-27 /pmc/articles/PMC10052463/ /pubmed/36986461 http://dx.doi.org/10.3390/ph16030361 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Qian
Peng, Dewei
Huang, Bingyu
Men, Lintong
Jiang, Tao
Huo, Shengqi
Wang, Moran
Guo, Junyi
Lv, Jiagao
Lin, Li
Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice
title Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice
title_full Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice
title_fullStr Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice
title_full_unstemmed Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice
title_short Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice
title_sort notopterol ameliorates hyperuricemia-induced cardiac dysfunction in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052463/
https://www.ncbi.nlm.nih.gov/pubmed/36986461
http://dx.doi.org/10.3390/ph16030361
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